tbuckley/cabot-search huggingface dataset:
PB2545: HAEMATOLOGICAL INDICES IN DIFFERENTIAL DIAGNOSIS OF MICROCYTIC ANEMIAS, A REGIONAL STUDY
Authors: Rialda Myrtaj, Liri Seraj, Evriola Dede, Isrena Alushaj, Jonida Bego, Etleva Refatllari
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: The World Health Organization (WHO) defines anemia in adults as an Hb<12 g/dL for non-pregnant women and <13 g/dL for men. In older people, an Hb concentration <12 g/dL is usually considered an established diagnosis for anemia (under the strict meaning of academic definition), regardless of the patient’s gender. Aims: The purpose of this study is to compare and differentiate certain types of anemia in Fier County (such as Iron-deficiency anemia, Thalassemia minor, chronic disease anemia and combinations of these anemias) based on haematological parameters and ferritin. The aim is also to extract prevalence for each diagnosis. Methods: This is a study in retrospect. The study included patients who were first diagnosed with anemia in their routine checks during June 2021–April 2022 in Fier county. Statistical analysis for the implementation of this study was performed using SPSS. The patients were divided into 4 groups according to the type of anemia that appears. Continued data was evaluated using T test. The differences were considered statistically significative for P<0.05 values. Results: Most of patients taken in this study have been diagnosed with Iron-deficiency anemia (29%). The average age for each diagnosis are; Iron-deficiency anemia 36.27 years, Iron-deficiency anemia & Thalassemia minor 29 years, anemia of chronic disease 63.88 years. Women predominate in all groups taken in the study. Iron-deficiency anemia has a lower haemoglobin and a higher MCV compared to Thalassemia minor and co-existence of two anemias. RDW and MCV should be used combined to make differentiation of Thalassemia minor and Iron-deficiency anemia. The Mentzer index has a high sensitivity in differentiation of anemias. Ferritin can be a good test to differentiate Iron-deficiency anemia with thalassemia minor and mix anemia. There was not a significant relationship between the level of ferritin and RDW in Iron-deficiency anemia and that of Iron-deficiency anemia & thalassemia minor. Summary/Conclusion: Patients with thalassemia minor with a haemoglobin value less than 11 g/dl and an RDW above the rate should be suspected of co-association with Iron-deficiency anemia. A moderate significant relationship was seen between the level of the urea and RBC, CRP, calcium, glycemia in chronic disease anemia, suggesting that in these patients we should also make assessments of these parameters. Keywords: beta thalassemia, Thalassemia, Iron deficiency anemia, Anemia
P1667: ATTRIBUTES OF RANDOMIZED CONTROLLED TRIALS AND THEIR ASSOCIATIONS WITH FUNDING SOURCE IN VENOUS THROMBOEMBOLISM PROPHYLAXIS FOR PATIENTS WITH CANCER: A BIBLIOGRAPHICAL ANALYSIS
Authors: Lucy Zhao, Jayhan Kherani, Pei Ye LI, Kevin Zhang, Angelina Horta, Christine Lin, Allen LI, Ali Eshaghpour, Mark Crowther
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Commercial sponsorship plays a large role in shaping the literature in hematology. Commercial sponsorship has potential to overcome feasibility limitations inherent in randomized controlled trials (RCTs), such as recruitment and duration of follow up, but may attract scrutiny in its robustness or potential for bias. Aims: In RCTs of venous thromboembolism (VTE) prophylaxis in patients with cancer, how do commercially sponsored RCTs compare with non-commercially funded RCTs regarding publication patterns such as reporting bias, robustness, and trial characteristics? Methods: OVID Medline, Embase, and Cochrane CENTRAL, were systematically searched for RCTs that investigated at least one pharmacologic intervention for VTE prophylaxis in adult patients with cancer. Article screening and data extrapolation were conducted in duplicate. Outcomes include a comprehensive set of trial characteristics (e.g. sample size, duration), a favourable outcome, the discrepancy between protocol and manuscript, and appraisal of “spin.” Outcomes were compared using the independent t-test, Mann-Whitney test, Pearson chi-squared test, and Fisher’s exact test where appropriate. Logistic regression was performed to identify factors associated with possible bias. Results: Of the 59 trials analyzed, 34 (63%) reported commercial sponsorship. Commercial sponsorship was not associated with the reporting of favourable outcomes, protocol-manuscript discrepancy, or presence of spin (Chi-squared=0.025, p=0.87; Chi-squared=3.07, p=0.08; Chi-squared=0.20, p=0.65). The commercially sponsored trials had a higher rate of intention-to-treat analysis (Chi-squared=12.2, p=0.0006). In contrast, non-commercially sponsored trials were likelier to report retrospective registration of trial protocol and use of composite primary outcomes (Chi-squared=9.8628, p=0.007; Chi-squared=3.88, p=0.05). Commercial sponsorship was not associated with presence of spin or high levels of spin (Chi-squared=0.20, p=0.65; Chi-squared = 2.52, p=0.11). Spin was most prevalent in the abstract conclusions (9 out of 17 [53.3%]) and manuscript conclusions (8 out of 17 [46.7%]). Summary/Conclusion: There were few significant differences in publication characteristics between commercially sponsored and non-commercially sponsored trials. These results suggest that the evidence from commercially sponsored trials investigating VTE prophylaxis in cancer patients is not likely to be subject to biases attributable to commercial sponsorship.Keywords: Venous thromboembolism, Anticoagulants, Thromboprophylaxis, Cancer
P1355: DELIVERY OF THERAPEUTIC RNA TO THE BONE MARROW IN MULTIPLE MYELOMA USING CD38-TARGETED LIPID NANOPARTICLES
Authors: Dana Tarab-Ravski, Iuliana Vaxman, Tamar Berger, Inbal Hazan-Halevy, Pia Raanani, Dan Peer
Journal: HemaSphere (2023)

Topic: 24. Gene therapy, cellular immunotherapy and vaccination - Biology & Translational Research Background: Multiple myeloma (MM) is a cancer of plasma cells that occurs in the bone marrow (BM). Despite the recent advancements in drug development for MM, most patients eventually relapse and there is a constant need for developing new therapeutic options for this disease. RNA-based therapies are an appealing therapeutic approach for cancer, as they hold the potential to manipulate the genetic expression of any gene and cell. However, clinical implementation of RNA therapy is limited due to inefficient systemic delivery of ribonucleotides to cells outside the liver, especially lymphocytes. Aims: We aim to generate a novel RNA-based therapy for MM by silencing the expression of crucial genes in MM cells and therefore lead to the alleviation of the disease. Methods: We utilize lipid nanoparticles (LNPs) as they are currently the most advanced and clinically approved non-viral delivery system of RNA. In this study, we present targeted (t)LNPs designed for delivery of RNA payload to MM cells. The tLNPs consists of a novel ionizable lipid and are coated with an anti-CD38 antibody (αCD38-tLNPs). To explore their therapeutic potential, we use small interference RNA (siRNA) to block the expression of cytoskeleton-associated protein 5 (CKAP5), a protein that regulates centrosomal organization during mitosis. Results: We demonstrate that LNPs encapsulating siRNA-CKAP5 lead to a significant decrease in cell viability upon transfection of MM cells in vitro and primary MM cells ex vivo. Next, since previously described xenograft MM mouse models have poor homing of MM cells to the BM and are therefore not suitable for evaluating the retention of systemically administered drugs to the BM, we establish a novel xenograft MM mouse model. Our new model clinically resembles the human disease as the MM-bearing mice display lytic bone lesion and secretion of monoclonal protein to the serum, and, importantly, demonstrate efficient homing of MM cells to the BM. Using this model, we show the specific delivery of αCD38-tLNPs to BM-residing and disseminated MM cells and the improvement in therapeutic outcome of MM-bearing mice treated with αCD38-tLNPs-siRNA-CKAP5. Summary/Conclusion: These results underscore the potential of RNA therapeutics for the treatment of MM and the importance of developing effective targeted delivery systems and reliable preclinical models.Keywords: Nanoparticle, Multiple myeloma, RNA interference (RNAi), Bone Marrow
P1101: A PROSPECTIVE TRIAL OF A NOVEL RECOMBINANT HUMANIZEDANTI-INTERLEUKIN-6 RECEPTOR MONOCLONAL ANTIBODY INJECTION(VDJ001) IN IDIOPATHIC MULTICENTRIC CASTLEMAN DISEASE: THE PRELIMINARY RESULTS
Authors: Lu Zhang, Yujun Dong, Xiao-Ming Gong, Xiao-Rui Zhang, Rong MA, Jian-Wei Cheng, Jun Zhang, Jian LI
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Interleukin-6 (IL-6) targeted therapy has been recommended as the most important treatment option for idiopathic Multicentric Castleman Disease (iMCD). However, the effective rate of siltuximab, the mostly widely used IL-6 targeted therapy for iMCD, was not satisfactory (34% in clinical trial). Aims: The aim of this study was to explore the safety and efficacy of a novel recombinant humanized anti-interleukin-6 receptor monoclonal antibody (Anti-IL-6R mAb) injection (VDJ001) in iMCD. Methods: A total of 9 iMCD patients with active disease were enrolled in this single-arm, open-label, multicenter, dose-escalation study from April, 2022 to September, 2022. All patients received VDJ001 infusion (4mg/kg dose, n=3; 6mg/kg dose, n=3; 8mg/kg dose, n=3) every 2 weeks and each infusion was considered as a cycle. Safety profiles were recorded by Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. Treatment responses were evaluated according to the Castleman Disease Collaborative Network (CDCN) criteria. As a preliminary analysis, this report collected data before January 31, 2023. Results: The median age of 9 patients at the time of enrollment was 42 (29-52) years old, and the male to female ratio was 2:1. By the time of January 31, 2023, a median of 13 cycles (26 weeks) (range: 8-19 cycles) of treatment were given to patients. All patients had received more than 4 cycles of VDJ001 infusion (8 weeks); 6 patients had received more than 10 cycles of study drug (20 weeks). There were no Grade 3 or above adverse events (AE) in 4mg/kg subgroup. In 6mg/kg subgroup, one patient experienced Grade 3 neutropenia and Grade 3 lymphopenia while other patients did not have Grade 3 or above AEs. In 8mg/kg subgroup, only one patient had Grade 3 or above AE (Grade 3 eosinophilia). There was no discontinuation of study drug administration caused by AEs and there were no treatment-related deaths. The overall response rate was 55.6% at Week 8 (n=9) and 100% at Week 20 (n=6) (Figure 1A). There were significant improvements in CRP, hemoglobin level and albumin levels after VDJ001 treatment (Figure 1B). Summary/Conclusion: VDJ001, a novel recombinant humanized anti-IL-6R mAb, showed excellent safety and efficacy profiles in iMCD patients. Figure 1. Treatment response of iMCD patients after VDJ001 treatment. A. Treatment response evaluated with CDCN criteria; B. Change in median CRP, hemoglobin and albumin levels. Median and range are labeled with dots and lines.Keywords: IL-6, Castleman’s disease
PB1746: EVOLUTION OF SARS-COV-2 INFECTION IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Hamida Khémiri Guerbouj, Marwa Bahri, Amine Ben Moussa, Bizid Inaam, Manel Hamdoun Zahmoul, Hela Hannechi Rejeb, Olfa Bahri, Raihane Ben Lakhal, Yosr Ben Abdennabi, Lamia Aissaoui
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Children with hematological malignancies, including Acute Lymphoblastic Leukemia (ALL), are a serious risk factor for COVID-19. Aims: The aim of the work was to study the epidemiological, clinical, therapeutic and evolution of patients (children and adolescents) who had SARS-CoV-2 infection during their management and survival. Methods: It’s a retrospective, monocentric study, done in the Haematology Clinic for Children of Aziza Othmana’s Hospital (HAO) in Tunis from 1st October 2020 to 30th September 2021. Results: We collected 33 patients with a sex ratio of 0.94. Our population was relatively young with a median age of 11 years. No specific symptoms were found in our patients compared to the general population. SARS-CoV-2 infection was asymptomatic in 42.4% of our patients. The main clinical signs were fever and tachycardia in 57,6% then rhinorrhea in 52% and myalgia, cough and diarrhea in 33,5%. Neutropenia (all grades) was noted in 20 patients (60.6%), lymphopenia (lymphocytes<1500/mm3) was found in 23 patients (69.7%), anemia in 19 patients (57.6%) and thrombocytopenia (all grades) in 14 patients (42.5%). Only one patient had a severe form. 15 patients required hospitalization, two of them were in Intensive Care Unit (ICU). The mortality rate was 9%. The study showed that the status of the disease influences overall survival. This factor predicts mortality for patients in progression of the disease (p=0.00). In univariate study, the other mortality predictors were: Severity of COVID-19 infection (p=0.00) and C-reactive protein (CRP) rate>50mg/L (p=0.05). Summary/Conclusion: Despite the small sample, this work allowed us a comparison of the results with the literature, a contribution to recent publications, to implement Tunisian recommendations, after having established a national register of LAL and the development of a computerized system for the collection of data facilitating multicenter work. Keywords: Hematological malignancy, Acute lymphoblastic leukemia, COVID-19
PB2242: ACUTE LYMPHOBLASTIC LEUKEMIA SECONDARY TO ESSENTIAL THROMBOCYTHEMIA: SYSTEMATIC REVIEW AND META-ANALYSIS OF CASE REPORTS
Authors: Mihnea-Alexandru Găman
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Essential thrombocythemia (ET) rarely transforms into acute leukemia, and when this phenomenon occurs ET mostly evolves into acute myeloid leukemia. However, exceptional cases of acute lymphoblastic leukemia (ALL) transformed from ET have been reported. Aims: To present of overview of ET cases transformed into ALL by means of a systematic review and meta-analysis of case reports. Describe the epidemiology, clinical and laboratory findings, diagnostic instruments, therapy and outcomes of these cases. Methods: Systematic search executed in PubMed/Medline from its inception until 01.03.2023, to identify papers written in English tackling this research question. Eligibility criteria: 1. Confirmed diagnosis of ET, 2. Confirmed diagnosis of ALL, 3. Availability of full-texts and information on the selected outcomes. Results: The systematic search retrieved 403 potentially relevant manuscripts. Following removal of reviews and other irrelevant papers and screening of abstracts/titles (n=397), 6 manuscripts were chosen for full-text review. After applying the eligibility criteria, 6 papers were entered into the qualitative and quantitative analysis. Transformation of ET into ALL was reported in 6 cases: 67% females, mean age at ET diagnosis 66 years, age range 49-87 years. The papers were published between 1995 and 2022 and came from The United States of America (n=2), Japan, Ireland, New Zealand and The United Kingdom (n=1 each). ET transformed into ALL in about 7.6 years (range 1-26 years), particularly ALL of B-cell lineage (n=4, 67%). ALL diagnosis was established based on bone marrow assessment and flow-cytometry. Cytogenetics and molecular genetics studies were performed in most cases, with cytogenetics frequently identifying additional chromosomal aberrations. Initial ET treatment consisted in hydroxyurea in all cases, in association with aspirin as antiplatelet agent. CALR and MPL mutations were detected in 2 cases and 1 case, respectively, whereas 1 case was triple negative (including for JAK2 mutations). ALL was treated with chemotherapy in 4 cases and with supportive care in 2 cases. Death occurred in 2 cases of ALL post-ET, whereas complete remission without eradication of the ET clone was achieved in 4 cases. The attached table summarizes the findings of this meta-analysis of case reports.Summary/Conclusion: Although transformation of ET into acute leukemia occurs rarely and mostly into AML, peculiar cases of post-ET ALL have been reported. ALL transformed from ET seems to develop primarily in females, the elderly, in patients treated with hydroxyurea, emerge mostly of B-cell lineage and be associated with additional cytogenetic and molecular abnormalities. Chemotherapy is able to induce complete remission of ALL, however, without eradication of the ET clone. Keywords: Essential Thrombocytemia, Acute lymphoblastic leukemia, B cell acute lymphoblastic leukemia, Myeloproliferative disorder
Transplantation after CD45-ADC corrects Rag1 immunodeficiency in congenic and haploidentical settings
Authors: Francesca Pala, Cristina Corsino, Enrica Calzoni, Anna Villa, Stefania Pittaluga, Rahul Palchaudhuri, Marita Bosticardo, Luigi D. Notarangelo
Journal: Journal of Allergy and Clinical Immunology (2023)
PB2451: EVALUATION OF PLATELET PARAMETERS IN PATIENTS WITH SECONDARY FAILURE OF PLATELET RECOVERY AND CYTOMEGALOVIRUS INFECTION AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Yigeng Cao, Aiming Pang, Erlie Jiang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Secondary failure of platelet recovery (SFPR) is a serious complication after hematopoietic stem cell transplantation (HSCT) and the significance of platelet parameters in SFPR remains unclear. Moreover, the role of CMV infection in SFPR is unclear and the correlation between platelet parameters and CMV infection in patients with SFPR is unknown. Aims: To investigate the clinical significance of changes in platelet parameters in patients with secondary failure of platelet recovery (SFPR) and cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). Methods: In this retrospective study, 79 patients who had undergone allogeneic HSCT (allo-HSCT), including 40 patients with SFPR, between January 2017 and September 2019 at the Stem Cell Transplantation Center of the Hematology Hospital (Institute of Hematology), Chinese Academy of Medical Sciences were included. The evaluated parameters were platelet count (PLT), plateletcrit (PCT), platelet-large cell ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), incidence of CMV infection after allo-HSCT, and the correlation of SFPR and CMV infection in patients who had undergone allo-HSCT. The control group included 107 healthy donors. Results: The SFPR group had significantly lower megakaryocyte counts, PLT, and PCT and significantly higher P-LCR, MPV, and PDW than the healthy donor and non-SFPR groups. The incidence of CMV infection was higher in SFPR patients than in non-SFPR patients. Among the patients with SFPR, P-LCR, MPV, and PDW were lower in those with CMV DNA >8000 copies/mL than in those with CMV DNA <8000 copies/mL (p < 0.05 for all); the CMV viral load was slightly negatively correlated with MPV (p = 0.0297) and P-LCR (p = 0.0280). Summary/Conclusion: The level of platelet activation in SFPR patients, which was closely related to CMV infection, was higher than that in that in non-SFPR patients, and higher CMV load was associated with the inhibition of platelet activation. Table. CMV infection in non-SFPR group and SFPR group - CMV infection Non-SFPR (n=39 ) SFPR(n=40) P value No CMV infection/case 32 11 CMV infection/case 7 29 CMV <8000(copies/mL)/case 6 24 CMV >8000(copies/mL)/case 1 5 CMV >8000(copies/mL)proportion(%) 14.2 17.2 the incidence of CMV infection（%） 17.9 72.5 P<0.0001 Average copy number(x±s)（copies/mL） 5452±6875.74 7024.21±9109.32 P=0.2022 CMV, Cytomegalovirus. Keywords: Platelet engraftment, Hematopoietic cell transplantation, Platelet activation
P1536: SARS-COV-2 INFECTIONS IN PATIENTS WITH HAEMATOLOGIC MALIGNANCIES: EFFECT OF VACCINATION AND THE DEVELOPMENT OF HYBRID IMMUNITY
Authors: Sabine Haggenburg, Tom Reuvekamp, Quincy Hofsink, Cilia R. Pothast, Romy C. Dijkland, Kayleigh van Dijk, Annoek E.C. Broers, Jaap van Doesum, Rob S. van Binnendijk, Gerco den Hartog, Michel S. Bhoekhan, Nienke J.E. Haverkate, Sandra Vogels-Nooijen, Inger S. Nijhof, Mirjam H.M. Heemskerk, Caroline E. Rutten, Abraham Goorhuis, Mette D. Hazenberg
Journal: HemaSphere (2023)
PB2568: BIERMER’S DISEASE REVEALED BY SPONTANEOUS ABORTIONS AND IRON DEFICIENCY ANEMIA: A CASE REPORT.
Authors: Hind Hanani, Yasmina Chhih, Hajar Khibri, Wafa Ammouri, Mouna Maamar, Hicham Harmouche, Zoubida Tazi Mezalek
Journal: HemaSphere (2023)

Topic: 29. Iron metabolism, deficiency and overload Background: Biermer’s disease can easily be diagnosed in the face of frankly macrocytic anemia. It can however present itself in a misleading array of intramedullary hemolysis, thrombophilia by hyperhomocysteinemia or thrombotic pseudo-microangiopathy. Aims: Describe Biermer’s disease’s polymorphism and principle of parsimony’s importance. Methods: Clinical case of a patient admitted for an anemic syndrome and diagnosed in an internal medicine department in 2022. Results: We report the case of a 27-year-old patient, with an anamnesis of three spontaneous miscarriages at 10 weeks of amenorrhea, admitted for exploration of an anemic syndrome. Clinical examination was normal. She presented on one hand a iron deficiency (ferritin: 17 ng/mL), on the other hand signs haemolysis’ signs. White blood cells, platelets and renal function were normal, with no schistocytes on smear. G6PD, pyruvate kinase and Coombs’ tests were normal and no PNH clone was found. Search for antiphospholipid antibodies as a cause of thrombophilia which could explain the spontaneous miscarriages was negative. As part of the iron deficiency’s etiological assessment, an upper digestive endoscopy showed moderately atrophic chronic funditis with intestinal metaplasia. Autoimmune gastritis secondary to Biermer’s disease resulting in hyperhomocysteinemia, intramedullary hemolysis and iron deficiency was then suspected. The assessment then requested revealed a vitamin B12 level of 120 ng/L, hyperhomocysteinemia of 44 micromoles/L and the presence of anti-parietal cell and anti-intrinsic factor antibodies. The patient was put on vitamin B12 and iron supplementation. Summary/Conclusion: Biermer’s disease polymorphism can mislead the clinician who should hence keep this diagnosis in mind. This clinical case also shows the importance of being unicist. Keywords: Iron deficiency anemia, Hemolysis, Thrombophilia